This Program Project examines structural and functional properties of membranes as they relate to the physiological, pharmacological, and pathophysiological behavior of heart and vascular smooth muscle. Studies of the control of ion fluxes, both active and passive, ligand binding, and the regulation of ion channels in both isolated and intact cell membranes are correlated with data regarding the structures of ligand- and metal ion-binding sites in artificial, reconstituted, and bioligical membranes. The effects of membrane hydrolysis, added amphiphiles and diet on membrane structure and function are examined in isolated cardiac sarcoplasmic reticulum and sarocolemma membranes, and intact cells. Intact cells are also used to examine interactions of calcium channel blockers and muscarinic agonists on cellular function, and the effects of altered surface charge on electrophysiological properties. The 10 projects and 3 cores are directed to an enhanced understanding of normal membrane functions, the mechanisms by which physiological neurotransmitters and drugs modify these functions, and the impact of diet and disease on membrane properties.